SummaryOver 12 years of cellular therapy in cardiology, some dictinct positive results are obtained in randomized studies. However, exact mechanisms of hematopoietic stem cell actions are still unclear under these clinical conditions. Paracrine effects of cell therapy cannot explain all these effects. Enhanced neoangiogenesis upon stem cell injection is a proven mechanism for improvement of blood supply to the heart. Meanwhile, a decreased revascularization effect 3-4 years after cell therapy is followed by repeated myocardial improvement 6-9 mo after repeated cell infusions with active development of collateral vessels, thus suggesting an additional mechanism for improvement of coronary blood supply. Restoration of regulatory functions of endothelium and smooth muscle cells, including increased NO synthase activity of endothelium and its interactions with myocardiocytes may represent a probable mechanism for this action.

Introduction. Chronic thromboembolic pulmonary hypertension (CTEPH) is one of the most severe complications of pulmonary embolism (PE), characterized by poor prognosis and insuffcient effectiveness of standard treatment approaches. A small number of representative models of CTEPH make it diffcult to conduct preclinical studies of promising pharmacological substances.Objective – development and validation of the experimental model of CTEPH in rats by embolization of the distal branches of the pulmonary artery with biodegradable microspheres.Material and methods. Male Wistar rats were used for the experiments. Biodegradable microspheres (MS) based on sodium alginate and autologous blood clots (AT) were used as embolizing particles. The animals were divided into groups: control: saline solution was injected 4 times with an interval of 8 days into the tail vein; AT: according to the above protocol, 50 μL of AT was injected; MS was administered intravenously in a volume of 50 μl of MS according to two protocols: MS4: 4 times with an interval of 8 days; MS8: 8 times with an interval of 4 days. After 2 and 6 weeks after the last injection, a histological examination of the lungs was performed; after 6 weeks: echocardiographic study (TTE), right ventricular catheterization (RV) with measurement of right ventricular systolic pressure (RVSP), treadmill test, assessment of serum endothelin­1 levels by the immunoassay method.Results. During the experiments, the survival rate in the MS8 group was 50 %. In the other groups, there were no animal losses. According to the treadmill test 6 weeks after the modeling of PE, exercise tolerance was signifcantly reduced in the MC4 and MC8 groups compared with the control group. TTE data indicate a signifcant increase in the diameter of the pulmonary trunk and the right ventricular outflow tract in the MC8 compared with the control and AT. There were signifcant increase in RVSP and the level of endothelin­1 compared with the control only in the MS8. After 6 weeks, the index of hypertrophy of vessel wall of the pulmonary artery in the MC4 and MC8 was signifcantly higher compared with the control and AT groups.Conclusion. Based on the use of MS, administered under the MS 8 protocol, a new representative model of CTEPH has been created, which can be used to test promising pharmacological substances.

Введение. Несмотря на несомненные успехи в лечении пациентов с ишемической болезнью сердца (ИБС), пока не удается добиться существенного снижения смертности при данном заболевании. Учитывая это, в настоящий момент повсеместно ведутся работы в отношении исследования новых методик с целью увеличить эффективность уже существующих стандартов. Одной из таких перспективных методик является клеточная/регенеративная терапия аутологичными мононуклеарами костного мозга (АМНКМ). Однако несмотря на то что АМНКМ исследуются на протяжении более 10 лет, к настоящему моменту не получено однозначных данных по ряду вопросов. Цель. Провести оценку результатов трансплантации АМНКМ при выполнении операции аортокоронарного шунтирования (АКШ) в комбинированном лечении ИБС. Материалы и методы. Проанализированны данные 408 пациентов, поступивших в клинику с 2013-го по 2016 г. для планового хирургического лечения ИБС. В работу включено 117 человек согласно дизайну исследования. Проведена рандомизация в 3 группы: группа 0-операция АКШ и интрамиокардиальное введение 0,9% раствора NaCl-контрольная группа, группа 1-операция АКШ и интрамиокардиальное введение АМНКМ, группа 2-операция АКШ, интрамиокардиальное и внутришунтовое введение АМНКМ. Через 12 месяцев выполнена оценка динамики-функционального класса стенокардии напряжения и сердечной недостаточности, ЭхоКГ, speckle tracking (оценка степени деформации миокарда), тредмил-теста, теста с 6-минутной ходьбой, суточного мониторирования ЭКГ, опросников качества жизни, коронарографии. Качественные показатели рассчитаны при помощи критериев Пирсона (χ 2) и Фишера. Количественные показатели-критерии Краскела-Уоллиса и Вилкоксона. Для выявления определенных факторов тяжести и исследования однородности данных-факторный анализ. Для исследования ведущих характеристик, определяющих дифференцировку между группами, проведен дискриминантный анализ. Для анализа дисперсии с учетом различных факторов использовали модель дисперсионного анализа для зависимых выборок-Repeated Measures ANOVA. Результаты. В группах наблюдения повсеместно отмечено улучшение как систолической, так и диастолической функции миокарда. Тест с 6-минутной ходьбой показал статистически значимый прирост в группах 1 и 2 по сравнению с контролем:

The in silico modelling of peptides complementary to lactoferrin was carried out using the Protein 3D software package and replication of the natural bonding site between pneumococcal surface protein (PSP) and lactoferrin (LF). The modeling was based on analysis of the conjugated ion–hydrogen bond systems between these proteins (CIHBS). The oligopeptide EEVAPQAQAKIAELENQVHRLE was proposed via computer modelling and synthesized using the solid phase synthesis technique, purified, and analyzed with MS and HPLC methods to confirm >95% purity. The peptide was then studied by capillary electrophoresis (CE). The CE experiments demonstrated the split of peptide zone in the presence of LF, due to complex formation and subsequent mobility change of the system peptide-protein. The reference experiments with homomyeloperoxidase and myoglobin did not show binding with LETI-11.

Chronic thromboembolic pulmonary hypertension (CTEPH) develops in 1.5–2.0% of patients experiencing pulmonary embolism (PE) and is characterized by stable pulmonary artery obstruction, heart failure, and poor prognosis. Little is known about involvement of autonomic nervous system (ANS) in the mechanisms of CTEPH. This study was aimed at evaluation of the effect of vagal and sympathetic denervation, as well as stimulation of the parasympathetic nervous system, on the outcomes of CTEPH in rats. CTEPH was induced by multiple intravenous injections of alginate microspheres. Sympathetic and vagal denervation was performed using unilateral surgical ablation of the stellate ganglion and vagotomy, respectively. Stimulation of the parasympathetic nervous system was carried out by administering pyridostigmine. The effect of neuromodulatory effects was assessed in terms of hemodynamics, histology, and gene expression. The results demonstrated the key role of ANS in the development of CTEPH. Sympathetic denervation as well as parasympathetic stimulation resulted in attenuated pulmonary vascular remodeling. These salutary changes were associated with altered MMP2 and TIMP1 expression in the lung and decreased FGFb level in the blood. Unilateral vagotomy had no effect on physiological and morphological outcomes of the study. The data obtained contribute to the identification of new therapeutic targets for CTEPH treatment.